Chlamydia trachomatis is the leading cause of bacterial sexually transmitted disease worldwide. Untreated genital chlamydial infections cause serious sequelae such as pelvic inflammatory disease, ectopic pregnancy, and infertility. A licensed vaccine, which is considered to be the ideal way to limit Chlamydia-induced morbidity, is currently not available. Chlamydial protease- like activity factor (CPAF) is a highly conserved bacterial protein secreted into the host cytosol. Our laboratory has shown the protective efficacy of intranasal vaccination with recombinant(r) CPAF (serovar L2) against genital chlamydial infection and pathology in mice. This protection is mediated by antigen-specific CD4+ T cells and highly dependent on the induction of endogenous IFN-3. Given (1) our extensive immunological characterization of rCPAF vaccination in conferring protective immunity against genital chlamydial infection in the mouse model, and (2) that the pathogenesis and immunity to chlamydial infection in guinea pigs has been shown to be remarkably similar to chlamydial genital infection in humans, we hypothesize that "vaccination with rCPAF will induce protective immunity against inflammatory pathology induced by genital chlamydial infection in guinea pigs". We propose to translate and validate the protective efficacy of rCPAF in an alternative animal model the guinea pig with C. caviae, the causative agent of guinea pig inclusion conjunctivitis (GPIC). The results obtained from these findings will provide important insights into the design of an effective anti-chlamydial vaccine for human use. This study will enable propogation of the guinea pig model of genital chlamydial infection established by Dr. Roger Rank (letter of support), which has been put to limited use in translational vaccine studies. Moreover, the completion of the sequencing of the guinea pig genome will result in the development of immunological reagents for characterization, which will further facilitate the use of this animal model in the scientific community. PUBLIC HEALTH RELEVANCE: Chlamydia trachomatis is the leading cause of bacterial sexually transmitted disease worldwide, and lead to severe pathology in the upper genial tract including pelvic inflammatory disease, ectopic pregnancy, and infertility. Immunization with chlamydial protease-like activity factor induces robust protective immunity against chlamydial infection and reproductive pathology in mice, justifying the further validation of this protective antigen. This proposal will further examine the potential of CPAF as a vaccine candidate against genital chlamydial infection in another species, the guinea pig. .